"Cancer is the leading cause of death in the developed world. Significant emphasis has recently been placed on the characterization of the human cancer genome. However, the genetic complexity of cancer has complicated the identification of driver mutations among the more abundant passenger mutations found in tumours. Forward genetic screens are powerful methods to identify genes involved in specific biological processes like cancer formation. However the difficulties and costs currently associated to such screens in vivo in mammalian systems are equally enormous.Here I propose the creation of a novel site-directed gene transfer system, allowing efficient and controlled somatic gene transfer in vivo in mice. This approach offers the possibility for the rapid creation of large number of somatic clones, over-expressing target proteins, or carrying transgenes to trigger RNAi response against the targeted gene products.I plan to screen cancer related miR-based gene knockdown libraries in this system, for the identification of novel genes involved in suppressing tumour formation. Recent findings are emphasizing the role of genomic instability caused by errors of DNA repair in the development of cancer. Using candidate gene approach I would like to investigate such mechanisms by the help of the proposed in vivo test system."